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[表皮生长因子受体(EGFR)突变丰度的检测及临床意义]

[Detection and Clinical Significance of Abundance of EGFR Mutation].

作者信息

Shao Yi, Zhong Diansheng

机构信息

Department of Medical Oncology, Tianjin Medical University General Hospital, Tianjin 300052, China.

出版信息

Zhongguo Fei Ai Za Zhi. 2017 Aug 20;20(8):578-583. doi: 10.3779/j.issn.1009-3419.2017.08.13.

Abstract

Non-small cell lung cancer (NSCLC) patients, with sensitive epidermal growth factor receptor (EGFR) mutations react well to tyrosine kinase inhibitors (TKIs). However, the efficacy of TKIs on patients with the same mutant types differs dramatically. It is implied that the different quantities of mutant alleles could be one of the reasons underlying. Patients with high abundance of EGFR mutation might benefit more from TKIs. There are no universal standards for the definition of EGFR mutant abundance. Abundance could be semi-quantified according to the different sensitivities of detection methods, quantified with quantifying detection techniques such as digital PCR or next generation sequencing, or quantified based on the expression of mutant proteins. The different abundances of primary and metastatic diseases could reflect the heterogeneity of the tumors. The pre-treatment level or the dynamic change of EGFR mutant abundance could help observe the course of the diseases and predict the efficacy of TKIs. TKIs resistance could be detected by change of abundance prior to image manifestations. Besides, the abundance of T790M could also predict drug efficacy and resistance of the first and third generation TKIs. Thus the detection of EGFR mutant abundance has important clinical significance. The standardization and correction of abundance needs more exploration.

摘要

非小细胞肺癌(NSCLC)患者中,具有敏感表皮生长因子受体(EGFR)突变的患者对酪氨酸激酶抑制剂(TKIs)反应良好。然而,TKIs对相同突变类型患者的疗效差异很大。这意味着不同数量的突变等位基因可能是其潜在原因之一。EGFR突变丰度高的患者可能从TKIs中获益更多。目前尚无EGFR突变丰度定义的通用标准。丰度可根据检测方法的不同敏感性进行半定量,用数字PCR或下一代测序等定量检测技术进行定量,或基于突变蛋白的表达进行定量。原发疾病和转移疾病的不同丰度可反映肿瘤的异质性。EGFR突变丰度的治疗前水平或动态变化有助于观察疾病进程并预测TKIs的疗效。在影像学表现出现之前,可通过丰度变化检测TKIs耐药性。此外,T790M的丰度也可预测第一代和第三代TKIs的药物疗效和耐药性。因此,EGFR突变丰度的检测具有重要的临床意义。丰度的标准化和校正还需要更多探索。

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